The traditional view of G protein-coupled receptors (GPCRs) has been that ligands, whether agonists or antagonists, affected both the G protein-dependent and β-arrestin-dependent pathways equally. Recently, however, it has been shown that the two pathways are pharmacologically separable. Certain ligands are capable of selectively activating one of the two pathways. These ligands are referred to as biased ligands, and the phenomenon is termed “biased agonism” or “ligand-directed signaling.” To date, no compounds or methods for identifying compounds that selectively activate one of the two pathways have been provided. Therefore, what is needed in the art are such compounds that have biased effects for treating β-arrestin and/or GPCR mediated responses, as well as methods of screening for such compounds. In addition, methods of using such ligands to treat conditions associated with the G protein-dependent and/or β-arrestin-dependent pathways are needed.